The goal of this project is to provide a molecular framework through which to analyze B and T lymphocyte differentiation and function. Initially, this has involved measuring the differences in gene expression between transformed cell lines and hybridomas which represent distinct types of B cells and T cells. These measurements demonstrate that each of these cells is very closely related and provide an important numerical basis for subsequent cloning experiments. Additionally, we developed an approach to preparing cloned cDNA libraries representing different cell type specific genes based on the use of selected cDNAs. Through this technique, we now have both B and T cell specific cDNA libraries, approximately 40 x enriched for the relevant sequences. We found that these libraries enabled the isolation of genes expressed at only a few mRNAs per cell. With this technology now in hand, we have begun to use it in the isolation of specific genes and address immunological problems. In particular we have mapped, isolated and sequenced an Ia gene (Ad/alpha), starting with genomic clones provided by Drs. M. Steinmetz and L. Hood of the California Institute of Technology. We have also identified an X-linked gene family which appears to be a maturational marker in B cells and may serve a similar function in T cells. This new gene complex may be particularly interesting in view of the numerous X-linked immunodeficiency diseases which exist. Finally, we have used this technique to analyze T cell specific cell surface receptor(s) and markers.